Farmacoriflessioni
Gli antistaminici di nuova generazione: quando, come, perché
NEW GENERATION ANTIHISTAMINES: WHEN, HOW, WHY
Bianca Lattanzi1, Arcangela Guerrieri2, Fernando Maria de Benedictis1
1Dipartimento di Pediatria, Azienda Ospedaliero-Universitaria, Ancona
2Pediatra di famiglia, Ancona
Ottobre 2008 - pagg. 511 -519
Abstract
Second-generation antihistamines differ from first-generation because of their elevated
specificity and affinity for peripheral H1-receptors and because of their lower penetration
in to the central nervous system, having fewer sedative effects as a result. Over the last few
years, new compounds with different pharmacokinetic properties have been synthesized.
The majority of these exhibit anti-inflammatory properties that are independent of their action
on the H1-receptors. More recent improvements of the molecules, generally in the form
of active metabolites, led to the synthesis of new-generation antihistamines. In the past, the
pharmacokinetics and pharmacodynamics of H1 antihistamines were not optimally investigated
in the pediatric population, especially in infants and young children. The pharmacology
of second-generation H1 antihistamines has been investigated relatively deeper
than old antihistamines in children, but a major attention to this aspect should be reserved
in future studies. In this article, the pharmacokinetic and pharmacodynamic characteristics
of the new oral antihistamines are described. Furthermore, their side effects, safety and the
clinical use in different allergic conditions in childhood are considered.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
1. Simons FE. Advances in H1-antihistamines.
N Engl J Med 2004;351:2203-17.
2. Bachert C. The role of histamine in allergic disease: re-appraisal of its inflammatory potential. Allergy 2002;57:287-96.
3. Marone G, Granata F, Spadaro G, Genovese A, Triggiani M. The histamine-cytokine network in allergic inflammation. J Allergy Clin Immunol 2003;112(Suppl 4):583-8.
4. Akdis CA, Blaser K. Histamine in the immune regulation of allergic inflammation. J Allergy Clin Immunol 2003;112:15-22.
5. Simons FE. Comparative pharmacology of H1 antihistamines: clinical relevance. Am J Med 2002;113:Suppl 9:38S-46S.
6. Holgate ST, Canonica GW, Simons FE, et al. Consensus Group on New Generation Antihistamines (CONGA): present status and recommendations. Clin Exp Allergy 2003;33: 1305-24.
7. Leurs R, Church MK, Taglialatela M. H1- antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy 2002;32:489-98.
8. Mullol J, Roca-Ferrer J, Alobid I, et al. Effect of desloratadine on epithelial cell granulocyte- macrophage colony-stimulating factor secretion and eosinophil survival. Clin Exp Allergy 2006;36:52-8.
9. Cyr MM, Hayes LM, Crawford L, Baatjes AJ, Keith PK, Denburg JA. The effect of desloratadine on eosinophil/basophil progenitors and other inflammatory markers in seasonal allergic rhinitis: a placebo-controlled randomized study. Int Arch Allergy Immunol 2005;138:209-16.
10. Agrawal DK. Anti-inflammatory properties of desloratadine. Clin Exp Allergy 2004;34: 1342-8.
11. Asano K, Kanai KI, Suzaki H. Suppressive activity of fexofenadine hydrochloride on metalloproteinase production from nasal fibroblasts in vitro. Clin Exp Allergy 2004;34:1890- 8.
12. Wu P, Mitchell S, Walsh GM. A new antihistamine levocetirizine inhibits eosinophil adhesion to vascular cell adhesion molecule-1 under flow conditions. Clin Exp Allergy 2005; 35:1073-9.
13. Ciprandi G, Cirillo I, Vizzaccaro A, Tosca MA. Levocetirizine improves nasal obstruction and modulates cytokine pattern in patients with seasonal allergic rhinitis: a pilot study. Clin Exp Allergy 2004;34:958-64.
14. Steinbrook R. Testing medication in children. N Engl J Med 2002;347:1462-70.
15. Simons FE. H1 antihistamines in children. In: Simons FE (Ed). Histamine and H1 antihistamines in allergic diseases. 2nd Ed, New York: Marcel Dekker Inc, 2002:437-64.
16. Gillard M, Christophe B, Wels B, Peck M, Massingham R, Chatelain P. H1 antagonists: receptor affinity versus selectivity. Inflamm Res 2003;52:S49-50.
17. Passalacqua G, Canonica GW. A review of the evidence from comparative studies of levocetirizine and desloratadine for the symptoms of allergic rhinitis. Clin Ther 2005;27: 979-92.
18. Banfield C, Hunt T, Reyderman L, Statkevich P, Padhi D, Affrime M. Lack of clinically relevant interaction between desloratadine and erythromycin. Clin Pharmacokinet 2002; 41:29-35.
19. Banfield C, Herron J, Keung A, Padhi D, Affrime M. Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole. Clin Pharmacokinet 2002;41:37-44.
20. Gupta S, Khalilieh S, Kantesaria B, Banfield C. Pharmacokinetics of desloratadine in children between 2 and 11 years of age. Brit J Clin Pharmacol 2007;63:534-40.
21. Gupta S, Kantesaria B, Banfield C, Wang Z. Desloratadine dose selection in children aged 6 months to 2 years: comparison of population pharmacokinetics between children and adults. Brit J Clin Pharmacol 2007;64:174-84.
22. Meltzer EO, Gillman SA. Efficacy of fexofenadine vs desloratadine in suppressing histamine- induced wheal and flare. Allergy Asthma Proc 2007;28:67-73.
23. Deruaz C, Leimgruber A, Berney M, Pradervand E, Spertini F. Levocetirizine better protects than desloratadine in a nasal provocation with allergen. J Allergy Clin Immunol 2004;113:669-76.
24. Lee DK, Gardiner M, Haggart K, Fujihara S, Lipworth BJ. Comparative effects of desloratadine, fexofenadine, and levocetirizine on nasal adenosine monophosphate challenge in patients with perennial allergic rhinitis. Clin Exp Allergy 2004;34:650-3.
25. Russell T, Stoltz M, Weir S. Pharmacokinetics, pharmacodynamics, and tolerance of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers. Clin Pharmacol Ther 1998;64:612-21.
26. Simons FER, Bergman JN, Watson WTA, Simons KJ. The clinical pharmacology of fexofenadine in children. J Allergy Clin Immunol 1996;98:1062-4.
27. Simons FE, Semus MJ, Goritz SS, Simons KJ. H1 antihistaminic activity of cetirizine and fexofenadine in allergic children. Pediatr Allergy Immunol 2003;14:207-11.
28. Strolin-Benedetti M, Plisnier M, Kaise J, et al. Absorption, distribution, metabolism and excretion of [14C] levocetirizine, the R enantiomer of cetirizine, in healthy volunteers. Eur J Clin Pharmacol 2001;57:571-82.
29. Simons FE, Simons KJ. Levocetirizine: pharmacokinetics and pharmacodynamics in children age 6 to 11 years. J Allergy Clin Immunol 2005;116:355-61.
30. Cranswick NE, Turzikova J, Fuchs M, Hulhoven R. Levocetirizine in 1-2 year old children: pharmacokinetic and pharmacodynamic profile. Int J Clin Pharmacol Ther 2005; 43:172-7.
31. Simons FE, for the ETAC Study Group. Population pharmacokinetics of levocetirizine in very young children: the pediatricians’ perspective. Pediatr Allergy Immunol 2005;16:97- 103.
32. Simons FE. H1 antihistamines: more relevant than ever in the treatment of allergic disorders. J Allergy Clin Immunol 2001;108: S147-334.
33. Hindmarch I, Shamsi Z, Stanley N, Fairweather DB. A double-blind, placebo-controlled investigation of the effects of fexofenadine, loratadine and promethazine on cognitive and psychomotor function. Br J Clin Pharmacol 1999;48:200-6.
34. Barbey JT, Anderson M, Ciprandi G, et al. Cardiovascular safety of second-generation antihistamines. Am J Rhinol 1999;13:235-43.
35. Simons FER, on behalf of the ETAC Study Group. Prevention of acute urticaria in young children with atopic dermatitis J Allergy Clin Immunol 2001;107:703-6.
36. Simons FE, for the Early Prevention of Asthma in Atopic Children (EPAAC) Study Group. Safety of levocetirizine treatment in young atopic children: an 18-month study. Pediatr Allergy Immunol 2007;18:535-42.
37. Meltzer EO, Jalowayski AA, Vogt K, Iezzoni D, Harris AG. Effect of desloratadine therapy on symptom scores and measures of nasal patency in seasonal allergic rhinitis: results of a single-center, placebo-controlled trial. Ann Allergy Asthma Immunol 2006;96:363-8.
38. Simons FE, Prenner BM, Finn A, for the Desloratadine Study Group. Efficacy and safety of desloratadine in the treatment of perennial allergic rhinitis. J Allergy Clin Immunol 2003;111:617-22.
39. Kim K, Sussman G, Hebert J, Lumry W, Lutsky B, Gates D. Desloratadine therapy for symptoms associated with perennial allergic rhinitis. Ann Allergy Asthma Immunol 2006; 96:460-5.
40. Meltzer EO, Scheinmann P, Rosado Pinto JE, et al. Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis - a pooled analysis of three studies. Pediatr Allergy Immunol 2004;15:253-60.
41. Milgrom H, Kittner B, Lanier R, Hanpel F. Safety and tolerability of fexofenadine for the treatment of allergic rhinitis in children to 2 to 5 old. Ann Allergy Asthma Immunol 2007; 99:358-63.
42. de Blic J, Wahn U, Billard E, Alt R, Pujazon MC. Levocetirizine in children: evidenced efficacy and safety in a 6-week randomized seasonal allergic rhinitis trial. Pediatr Allergy Immunol 2005;16:267-75.
43. Potter PC, for the Paediatric Levocetirizine Study Group. Efficacy and safety of levocetirizine on symptoms and health-related quality of life of children with perennial allergic rhinitis: a double-blind, placebo-controlled randomized clinical trial. Ann Allergy Asthma Immunol 2005;95:175-80.
44. Potter PC, Bailey MJ, Bateman M, et al. Levocetirizine is effective for symptom relief including nasal congestion in adolescent and adult (PAR) sensitized to house dust mites. Allergy 2003;58:893-9.
45. Dizdar EA, Sekere BE, Keshin O, et al. The effect of regular versus on demand desloratadine treatment in children with allergic rhinitis. Int J Pediatr Otorinolaryngol 2007;71: 843-9.
46. Canonica GW, Compalati E, Guerra L, et al. Efficacy and safety of levocetirizine 5 mg as continuous or on-demand treatment for persistent allergic rhinitis over 6 months. XIX Congress of WAO. Munich, June 26-July 1, 2005 (Abstract).
47. Simons FE. H1-antihistamine treatment in young atopic children: effect on urticaria. Ann Allergy 2007;99:261-6.
48. Diepgen TL. Long-term treatment with cetirizine of infants with atopic dermatitis: a multicountry, double-blind, randomized, placebocontrolled trial (the ETAC trial) over 18 months. Pediatr Allergy Immunol 2002;13: 278-86.
49. Zuberbier T, Bindslev-Jensen C, Canonica W, et al. EAACI/GA2LEN/EDF guideline: management of urticaria. Allergy 2006;61:321-31.
50. Powell RJ, Du Toitw GL, Siddiquez N, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clin Exp Allergy 2007;37:631-50.
51. Klein PA, Clarke RA. An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch Dermatol 1999;135:1522-5.
52. Baena Cagnani CE, Berger WE, DuBuske LM, et al. Comparative effects of desloratadine vs montelukast on asthma symptoms and use of beta2-agonists in patients with seasonal allergic rhinitis and asthma. Int Arch Allergy Immunol 2003;130:307-13.
53. Warner JO. A double-blind, randomized, placebo-controlled trial of cetirizine in preventing the onset of asthma in children with atopic dermatitis: 18 months’ treatment and 18 months’ post treatment follow-up. J Allergy Clin Immunol 2001;108:929-37.
54. Warner J. Annual Congress of EAACI. Vienna, June 10-14, 2006. Personal communication.
55. Murdoch D, Goa KL, Keam SJ. Desloratadine: an update of its efficacy in the management of allergic disorders. Drugs 2003;63: 2051-77.
56. Simpson K, Jarvis B. Fexofenadine: a review of its use in the management of seasonal allergic rhinitis and chronic idiopatic urticaria. Drugs 2000;59:301-22.
57. Hair PI, Scott LJ. Levocetirizine. A review of its use in the management of allergic rhinitis and skin allergies. Drugs 2006;66:973-96.
2. Bachert C. The role of histamine in allergic disease: re-appraisal of its inflammatory potential. Allergy 2002;57:287-96.
3. Marone G, Granata F, Spadaro G, Genovese A, Triggiani M. The histamine-cytokine network in allergic inflammation. J Allergy Clin Immunol 2003;112(Suppl 4):583-8.
4. Akdis CA, Blaser K. Histamine in the immune regulation of allergic inflammation. J Allergy Clin Immunol 2003;112:15-22.
5. Simons FE. Comparative pharmacology of H1 antihistamines: clinical relevance. Am J Med 2002;113:Suppl 9:38S-46S.
6. Holgate ST, Canonica GW, Simons FE, et al. Consensus Group on New Generation Antihistamines (CONGA): present status and recommendations. Clin Exp Allergy 2003;33: 1305-24.
7. Leurs R, Church MK, Taglialatela M. H1- antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy 2002;32:489-98.
8. Mullol J, Roca-Ferrer J, Alobid I, et al. Effect of desloratadine on epithelial cell granulocyte- macrophage colony-stimulating factor secretion and eosinophil survival. Clin Exp Allergy 2006;36:52-8.
9. Cyr MM, Hayes LM, Crawford L, Baatjes AJ, Keith PK, Denburg JA. The effect of desloratadine on eosinophil/basophil progenitors and other inflammatory markers in seasonal allergic rhinitis: a placebo-controlled randomized study. Int Arch Allergy Immunol 2005;138:209-16.
10. Agrawal DK. Anti-inflammatory properties of desloratadine. Clin Exp Allergy 2004;34: 1342-8.
11. Asano K, Kanai KI, Suzaki H. Suppressive activity of fexofenadine hydrochloride on metalloproteinase production from nasal fibroblasts in vitro. Clin Exp Allergy 2004;34:1890- 8.
12. Wu P, Mitchell S, Walsh GM. A new antihistamine levocetirizine inhibits eosinophil adhesion to vascular cell adhesion molecule-1 under flow conditions. Clin Exp Allergy 2005; 35:1073-9.
13. Ciprandi G, Cirillo I, Vizzaccaro A, Tosca MA. Levocetirizine improves nasal obstruction and modulates cytokine pattern in patients with seasonal allergic rhinitis: a pilot study. Clin Exp Allergy 2004;34:958-64.
14. Steinbrook R. Testing medication in children. N Engl J Med 2002;347:1462-70.
15. Simons FE. H1 antihistamines in children. In: Simons FE (Ed). Histamine and H1 antihistamines in allergic diseases. 2nd Ed, New York: Marcel Dekker Inc, 2002:437-64.
16. Gillard M, Christophe B, Wels B, Peck M, Massingham R, Chatelain P. H1 antagonists: receptor affinity versus selectivity. Inflamm Res 2003;52:S49-50.
17. Passalacqua G, Canonica GW. A review of the evidence from comparative studies of levocetirizine and desloratadine for the symptoms of allergic rhinitis. Clin Ther 2005;27: 979-92.
18. Banfield C, Hunt T, Reyderman L, Statkevich P, Padhi D, Affrime M. Lack of clinically relevant interaction between desloratadine and erythromycin. Clin Pharmacokinet 2002; 41:29-35.
19. Banfield C, Herron J, Keung A, Padhi D, Affrime M. Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole. Clin Pharmacokinet 2002;41:37-44.
20. Gupta S, Khalilieh S, Kantesaria B, Banfield C. Pharmacokinetics of desloratadine in children between 2 and 11 years of age. Brit J Clin Pharmacol 2007;63:534-40.
21. Gupta S, Kantesaria B, Banfield C, Wang Z. Desloratadine dose selection in children aged 6 months to 2 years: comparison of population pharmacokinetics between children and adults. Brit J Clin Pharmacol 2007;64:174-84.
22. Meltzer EO, Gillman SA. Efficacy of fexofenadine vs desloratadine in suppressing histamine- induced wheal and flare. Allergy Asthma Proc 2007;28:67-73.
23. Deruaz C, Leimgruber A, Berney M, Pradervand E, Spertini F. Levocetirizine better protects than desloratadine in a nasal provocation with allergen. J Allergy Clin Immunol 2004;113:669-76.
24. Lee DK, Gardiner M, Haggart K, Fujihara S, Lipworth BJ. Comparative effects of desloratadine, fexofenadine, and levocetirizine on nasal adenosine monophosphate challenge in patients with perennial allergic rhinitis. Clin Exp Allergy 2004;34:650-3.
25. Russell T, Stoltz M, Weir S. Pharmacokinetics, pharmacodynamics, and tolerance of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers. Clin Pharmacol Ther 1998;64:612-21.
26. Simons FER, Bergman JN, Watson WTA, Simons KJ. The clinical pharmacology of fexofenadine in children. J Allergy Clin Immunol 1996;98:1062-4.
27. Simons FE, Semus MJ, Goritz SS, Simons KJ. H1 antihistaminic activity of cetirizine and fexofenadine in allergic children. Pediatr Allergy Immunol 2003;14:207-11.
28. Strolin-Benedetti M, Plisnier M, Kaise J, et al. Absorption, distribution, metabolism and excretion of [14C] levocetirizine, the R enantiomer of cetirizine, in healthy volunteers. Eur J Clin Pharmacol 2001;57:571-82.
29. Simons FE, Simons KJ. Levocetirizine: pharmacokinetics and pharmacodynamics in children age 6 to 11 years. J Allergy Clin Immunol 2005;116:355-61.
30. Cranswick NE, Turzikova J, Fuchs M, Hulhoven R. Levocetirizine in 1-2 year old children: pharmacokinetic and pharmacodynamic profile. Int J Clin Pharmacol Ther 2005; 43:172-7.
31. Simons FE, for the ETAC Study Group. Population pharmacokinetics of levocetirizine in very young children: the pediatricians’ perspective. Pediatr Allergy Immunol 2005;16:97- 103.
32. Simons FE. H1 antihistamines: more relevant than ever in the treatment of allergic disorders. J Allergy Clin Immunol 2001;108: S147-334.
33. Hindmarch I, Shamsi Z, Stanley N, Fairweather DB. A double-blind, placebo-controlled investigation of the effects of fexofenadine, loratadine and promethazine on cognitive and psychomotor function. Br J Clin Pharmacol 1999;48:200-6.
34. Barbey JT, Anderson M, Ciprandi G, et al. Cardiovascular safety of second-generation antihistamines. Am J Rhinol 1999;13:235-43.
35. Simons FER, on behalf of the ETAC Study Group. Prevention of acute urticaria in young children with atopic dermatitis J Allergy Clin Immunol 2001;107:703-6.
36. Simons FE, for the Early Prevention of Asthma in Atopic Children (EPAAC) Study Group. Safety of levocetirizine treatment in young atopic children: an 18-month study. Pediatr Allergy Immunol 2007;18:535-42.
37. Meltzer EO, Jalowayski AA, Vogt K, Iezzoni D, Harris AG. Effect of desloratadine therapy on symptom scores and measures of nasal patency in seasonal allergic rhinitis: results of a single-center, placebo-controlled trial. Ann Allergy Asthma Immunol 2006;96:363-8.
38. Simons FE, Prenner BM, Finn A, for the Desloratadine Study Group. Efficacy and safety of desloratadine in the treatment of perennial allergic rhinitis. J Allergy Clin Immunol 2003;111:617-22.
39. Kim K, Sussman G, Hebert J, Lumry W, Lutsky B, Gates D. Desloratadine therapy for symptoms associated with perennial allergic rhinitis. Ann Allergy Asthma Immunol 2006; 96:460-5.
40. Meltzer EO, Scheinmann P, Rosado Pinto JE, et al. Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis - a pooled analysis of three studies. Pediatr Allergy Immunol 2004;15:253-60.
41. Milgrom H, Kittner B, Lanier R, Hanpel F. Safety and tolerability of fexofenadine for the treatment of allergic rhinitis in children to 2 to 5 old. Ann Allergy Asthma Immunol 2007; 99:358-63.
42. de Blic J, Wahn U, Billard E, Alt R, Pujazon MC. Levocetirizine in children: evidenced efficacy and safety in a 6-week randomized seasonal allergic rhinitis trial. Pediatr Allergy Immunol 2005;16:267-75.
43. Potter PC, for the Paediatric Levocetirizine Study Group. Efficacy and safety of levocetirizine on symptoms and health-related quality of life of children with perennial allergic rhinitis: a double-blind, placebo-controlled randomized clinical trial. Ann Allergy Asthma Immunol 2005;95:175-80.
44. Potter PC, Bailey MJ, Bateman M, et al. Levocetirizine is effective for symptom relief including nasal congestion in adolescent and adult (PAR) sensitized to house dust mites. Allergy 2003;58:893-9.
45. Dizdar EA, Sekere BE, Keshin O, et al. The effect of regular versus on demand desloratadine treatment in children with allergic rhinitis. Int J Pediatr Otorinolaryngol 2007;71: 843-9.
46. Canonica GW, Compalati E, Guerra L, et al. Efficacy and safety of levocetirizine 5 mg as continuous or on-demand treatment for persistent allergic rhinitis over 6 months. XIX Congress of WAO. Munich, June 26-July 1, 2005 (Abstract).
47. Simons FE. H1-antihistamine treatment in young atopic children: effect on urticaria. Ann Allergy 2007;99:261-6.
48. Diepgen TL. Long-term treatment with cetirizine of infants with atopic dermatitis: a multicountry, double-blind, randomized, placebocontrolled trial (the ETAC trial) over 18 months. Pediatr Allergy Immunol 2002;13: 278-86.
49. Zuberbier T, Bindslev-Jensen C, Canonica W, et al. EAACI/GA2LEN/EDF guideline: management of urticaria. Allergy 2006;61:321-31.
50. Powell RJ, Du Toitw GL, Siddiquez N, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clin Exp Allergy 2007;37:631-50.
51. Klein PA, Clarke RA. An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch Dermatol 1999;135:1522-5.
52. Baena Cagnani CE, Berger WE, DuBuske LM, et al. Comparative effects of desloratadine vs montelukast on asthma symptoms and use of beta2-agonists in patients with seasonal allergic rhinitis and asthma. Int Arch Allergy Immunol 2003;130:307-13.
53. Warner JO. A double-blind, randomized, placebo-controlled trial of cetirizine in preventing the onset of asthma in children with atopic dermatitis: 18 months’ treatment and 18 months’ post treatment follow-up. J Allergy Clin Immunol 2001;108:929-37.
54. Warner J. Annual Congress of EAACI. Vienna, June 10-14, 2006. Personal communication.
55. Murdoch D, Goa KL, Keam SJ. Desloratadine: an update of its efficacy in the management of allergic disorders. Drugs 2003;63: 2051-77.
56. Simpson K, Jarvis B. Fexofenadine: a review of its use in the management of seasonal allergic rhinitis and chronic idiopatic urticaria. Drugs 2000;59:301-22.
57. Hair PI, Scott LJ. Levocetirizine. A review of its use in the management of allergic rhinitis and skin allergies. Drugs 2006;66:973-96.
Corrispondenza: debenedictis@ao-salesi.marche.it